Objectives: The expression of CD3, CD4, CD8, PD-1 and PD-L1 in mucosal malignant melanoma tumors was analyzed by immunohistochemical staining. The aim was to explore the characteristics of malignant melanoma in head and neck and its correlation with the expression of these factors, to further our understanding of the disease. Design:Retrospective clinical study. Setting: Otorhinolaryngology unit of a tertiary hospital. Participants: 36 patients underwent immunohistochemical staining. Main outcome measures: In total, 24 patients underwent immunohistochemical staining of CD4, CD8, PD-1, and PD-L1, and 12 patients underwent CD3 immunohistochemical staining. Results: There was no significant difference between the expression of CD3, CD4, or CD8 and the general clinical features of mucosal melanoma. However, (1) the high rate of expression of CD8 was significantly different in different lesion locations: 85.71% in the nasal cavity/sinus/nasal cavity and sinus, and 66.67% in the nasopharynx; (2) the expression of PD-L1 was statistically significantly correlated with the combined expression of CD4, CD8 and CD4/CD8 (r = 0.451, P < 0.05); (3) the median progression-free survival times of patients with high and low expression CD4 were 24 months and 4 months, respectively, and those of patients with high and low expression of CD8 were 24 months and 6 months, respectively. Conclusions: The correlation between the expression of CD8 and PD-L1 suggests the role of tumor infiltrating lymphocytes in anti-tumor immunity and their possible use as immunotherapy markers. In addition, the expression of CD4 and CD8 in tumor tissue may play a guiding role in the prognosis of patients.